The field of this invention is vascular disease, particularly vascular diseases characterized by the presence of calcified lesions, e.g. atherosclerosis.
The formation of plaques or lesions, (atherosclerotic plaques or lesions) on cardiovascular tissue, such as the inner surface of blood vessels, arotic valves, etc., is a major component of cardiovascular disease. Many atherosclerotic plaques and lesions are characterized by the presence of mineral desposits, i.e. they are calcified. Atherosclerotic calcification is thought to be an organized, regulated process similar to bone formation that occurs only when other aspects of atherosclerosis are also present. Calcium phosphate, in the crystalline form of carbonated apatite (dahllite), which contains 40% calcium by weight, precipitates in diseased coronary arteries by mechanisms that appear similar to that found in active bone formation and remodeling (Bostom, K., et al., J. Clin. Invest. 91:1800-9, 1993; Lowenstam, H. A., and Wiener, S., On Biomineralization, Oxford University Press, N.Y.). Atherosclerotic calcification begins as early as the second decade of life, just after fatty streak formation (Stary, H. C., Eur. Heart J. 11(Suppl. E):3-19, 1990). The lesions of younger adults have revealed small aggregates of crystalline calcium phosphate among the lipid particles of lipid cores (Stary, H. C., et al., Circulation 92:1355-74, 1995). Calcific deposits are found more frequently and in greater amounts in elderly individuals and more advanced lesions (Doherty, T. M., and Detrano, R. C., Calcif. Tissue Int. 54:224-30, 1994). In most advanced lesions, when mineralization dominates the picture, components such as lipid deposits and increased fibrous tissue may also be present.
Calcified lesion formation on prosthetic devices is also a problem in current cardiovascular disease treatment protocols. For example, calcification is an important limitation on the useful life expectancy of bioprosthetic valves, and accounts for over sixty percent of the cardiac bioprostheses failures.
A variety of different protocols have been developed for treating cardiovascular diseases associated with the presence of calcified lesions. Such treatment methodologies generally involve mechanical removal or reduction of the lesion and include: bypass surgery, balloon angioplasty, mechanical debridement, valve replacement, and the like. Despite the plethora of different treatment strategies that have been developed for the treatment of cardiovascular disease, there are disadvantages associated with each technique, such as tissue damage, invasiveness, etc. For example, restenosis is a common complication that results in arteries in which lesions have been mechanically removed.
As such, there is continued interest in the development of new treatment protocols for the removal of vascular calcified lesions from vascular tissue. Of particular interest would be the development of a treatment protocol that is minimally invasive and results in minimal tissue damage.
U.S. Patents of interest include: U.S. Pat. Nos. 4,636,195; 4,976,733; 5,222,941; 5,380,284; and 5,443,446. Other U.S. Patents of interest include: U.S. Pat. Nos. 4,445,892; 4,573,966; 4,610,662; 4,655,746; 4,824,436; 4,911,163; 5,059,178; 5,090,960; 5,167,628; and 5,195,955.
Methods and devices for at least reducing the mineral content of a calcified lesion on vascular tissue are provided. In the subject methods, the local environment of the target lesion is maintained at a subphysiologic pH for a period of time sufficient for the desired amount of demineralization to occur, e.g. by flushing the lesion with a fluid capable of locally increasing the proton concentration in the region of the calcified lesion. As a result, the mineral content of the calcified lesion is reduced. Also provided are catheters for use in the subject methods, where the subject catheters at least include a first lumen for introducing fluid to a vascular site and a second lumen for removing liquid from a vascular site, where the second lumen preferably has a cross-sectional dimension that is sufficiently large to allow passage of lesion debris. The subject methods and devices find use in the treatment of vascular diseases associated with the presence of calcified lesions.